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The incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed deathligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP.

Eligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10mg/kg intravenously every 2weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per phenrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.

Results from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.

The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS.

Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23-75 years from the Generations Study.

The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio (E/O) at the highest risk decile 0.97(95 % CI0.51 - 1.86) for women younger than 50 years and 1.09(0.66 - 1.80) for women 50 years o risk stratified breast cancer prevention among women of European ancestry.

Processing the surface electromyogram (sEMG) to decode movement intent is a promising approach for natural control of upper extremity prostheses. To this end, this paper introduces and evaluates a new framework which allows for simultaneous and proportional myoelectric control over multiple degrees of freedom (DoFs) in real-time. The framework uses multitask neural networks and domain-informed regularization in order to automatically find nonlinear mappings from the forearm sEMG envelope to multivariate and continuous encodings of concurrent hand- and wrist kinematics, despite only requiring categorical movement instruction stimuli signals for calibration.

Forearm sEMG with 8 channels was collected from healthy human subjects (N = 20) and used to calibrate two myoelectric control interfaces, each with two output DoFs. SBI-115 cell line The interfaces were built from (I) the proposed framework, termed Myoelectric Representation Learning (MRL), and, to allow for comparisons, from (II) a standard pattern recognition frameworky enabling myoelectric control with real-time performance superior to that of the current commercial standard for pattern recognition (as represented by LDA). It is thus postulated that the presented MRL approach can be of practical utility for muscle-computer interfaces.

The results suggest that MRL is able to successfully generate stable mappings from EMG to kinematics, thereby enabling myoelectric control with real-time performance superior to that of the current commercial standard for pattern recognition (as represented by LDA). It is thus postulated that the presented MRL approach can be of practical utility for muscle-computer interfaces.Therapy resistance is a major problem when treating cancer patients as cancer cells develop mechanisms that counteract the effect of therapeutic compounds, leading to fit and more aggressive clones that contribute to poor prognosis. Therapy resistance can be both intrinsic and/or acquired. These are multifactorial events, and some are related to factors including adaptations in cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), deregulation of key signaling pathways, drug efflux through ABC transporters, acquired mutations, evading apoptosis, and activation of DNA damage response among others. Among these factors, CSCs represent the major source of therapy resistance. CSCs are a subset of tumor cells that are capable of self-renewal and multilineage progenitor expansion that are known to be intrinsically resistant to anticancer treatments. Multiple clones of CSCs pre-exist, and some can adopt and expand easily to changes in the tumor microenvironment (TME) and/or in response to radio- and chemotherapy. A combination of both intrinsic and extrinsic factors contributes to CSC-mediated therapy resistance. In this review, we will focus on CSCs and therapy resistance as well as suggest strategies to eliminate CSCs and, therefore, overcome resistance. Video abstract.

Intracerebral hemorrhage (ICH) can induce excessive accumulation of reactive oxygen species (ROS) that may subsequently cause severe white matter injury. The process of oligodendrocyte progenitor cell (OPC) differentiation is orchestrated by microglia and astrocytes, and ROS also drives the activation of microglia and astrocytes. In light of the potent ROS scavenging capacity of ceria nanoparticles (CeNP), we aimed to investigate whether treatment with CeNP ameliorates white matter injury by modulating ROS-induced microglial polarization and astrocyte alteration.

ICH was induced in vivo by collagenase VII injection. Mice were administered with PLX3397 for depleting microglia. Primary microglia and astrocytes were used for in vitro experiments. Transmission electron microscopy analysis and immunostaining were performed to verify the positive effects of CeNP in remyelination and OPC differentiation. Flow cytometry, real-time polymerase chain reaction, immunofluorescence and western blotting were used to detect microglia polarization, astrocyte alteration, and the underlying molecular mechanisms.